Heart failure (HF) is a debilitating disease in which abnormal function of the heart leads to inadequately low perfusion of tissues and organs of the body. In the early stages of HF many compensatory mechanisms are employed to maintain proper perfusion of tissues and alleviate stress on the heart. Some examples of such mechanisms include activation of the renin-angiotensin-aldosterone system (RAAS) and blood volume redistribution via neural control. As HF progresses, not only can cardiac function worsen, but the compensatory mechanisms themselves can eventually become maladaptive and start contributing to the symptoms of HF. For example, overactivation of RAAS can lead to severe remodeling of the ventricles. A particularly severe form of heart failure is congestive heart failure (CHF), in which weak pumping of the heart, together with over-active compensatory mechanisms such as sympathetic outflow, can lead to build-up of fluids in the lungs.
Pulmonary edema is a swelling and/or fluid accumulation in the lungs. It represents one of the congestive symptoms of CHF. The poor cardiac function leads to impaired outflow from the lungs, which increases blood pressure in the lungs, especially if systemic organs are constricting and redistributing additional blood from the systemic to the pulmonary loop. The increased pressure within pulmonary circulation can cause leaking of the fluid into lung tissue and air sacs. This can lead to severe respiratory problems, such as shortness of breath. Shortness of breath is the number one symptom with which decompensated CHF patients present to the hospital (˜89%).
Current mainstream treatment of pulmonary edema is aimed at reducing total blood volume by administering a diuretic treatment, based on a belief that it is total volume overload which leads to worsening of HF symptoms. However, in many cases total volume overload might not be the cause of decompensation, and, therefore, diuretics may no longer be the optimal treatment and may even cause additional damage, such as worsening renal function.